Microphthalmia transcription factor (Mitf)

The microphthalmia (mi) gene encodes a transcription factor, Mitf, anuclear basic helixloophelix leucine zipper protein9, whichis essential for the development and survival of melanocytes. The transcription factor regulates the transcription of genes involved in melanin synthesis, including tyrosinase, TRP1 and TRP2. Heterozygous mutation of themigene results in Waardenburg syndrome type IIA, a pigmentary disorder with a white forelock and hearing loss. Homozygousmi-deficient mice show complete loss of melanocytes from skin, the choroid of the eye and the stria vascularis of the inner ear: they are deficient in mast cells and develop osteopetrosis. Melanocyte stimulating hormone (a-MSH) stimulates expression of Mitf.

Although most papers indicate that it is a useful melanocytic marker, the diagnostic specificity of Mitf for melanomas has been thrown into question by a study of a large range of normal tissues and neoplasms, showing immunoreactivity in a wide range of tumours2. Reactivity of histiocytes is a particular cause of concern7.